• Kunwei Niu, Long Yang, Wenjie Song, Zhengcai Liu, Juzheng Yuan, Hong Zhang, Wenjie Zhang, Jianlin Wang, and Kaishan Tao.
• Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
• Shock. 2023 Jul 1; 60 (1): 758375-83.

AbstractObjective: Histone deacetylase inhibitors (HDACIs) have been reported to improve survival in rats with hemorrhagic shock (HS). However, no consensus exists on the most effective HDACIs and their administration routes. We herein aimed to determine the optimal HDACIs and administration route in rats with HS. Methods: Survival analysis: In experiment I, male Sprague-Dawley rats were subjected to HS (mean arterial pressure [MAP] was maintained at 30-40 mm Hg for 20 min), and intravenously injected with the following agents (n = 8 per group): (1) no treatment, (2) vehicle (VEH), (3) entinostat (MS-275), (4) [ N -((6-(Hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide] (LMK-235), (5) tubastatin A, (6) trichostatin A (TSA), and (7) sirtinol. In experiment II, rats were intraperitoneally injected with TSA. Mechanism research: In experiments I and II, rats were observed for 3 h, after which blood samples and liver, heart, and lung tissues were harvested. Results: In experiment I, 75% rats in the VEH group but only 25% rats in the LMK-235 and sirtinol groups died within ≤5 h of treatment, whereas the survival of rats in the MS-275, tubastatin A, and TSA groups was significantly prolonged. MS-275, LMK-235, tubastatin A, and TSA significantly reduced histopathological scores, apoptosis cell numbers, and inflammatory cytokine levels. In experiment II, the survival was longer after i.v. TSA treatment than after i.p. TSA treatment, and the IL-6 levels in the heart were significantly lower in rat who received i.p. TSA treatment than in those who received i.v. TSA treatment. Conclusions: The i.v. effect was superior to the i.p. effect, while nonselective and isoform-specific classes I and IIb HDACIs had similar effects.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.

13 keywords...

hide…